1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Chapter 8 An Introduction to Metabolism

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics Metabolism is the totality of an organism’s chemical reactions

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Organization of the Chemistry of Life into Metabolic Pathways A metabolic pathway begins with a specific molecule and ends with a product Each step is catalyzed by a specific enzyme

4. LE 8-UN141 Enzyme 1 AB Reaction 1 Enzyme 2 C Reaction 2 Enzyme 3 D Reaction 3 Product Starting molecule

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Catabolic pathways release energy by breaking down complex molecules into simpler compounds Anabolic pathways consume energy to build complex molecules from simpler ones Bioenergetics is the study of how organisms manage their energy resources

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Forms of Energy Energy is the capacity to cause change Energy exists in various forms, some of which can perform work

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Kinetic energy is energy associated with motion – Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules Potential energy is energy that matter possesses because of its location or structure – Chemical energy is potential energy available for release in a chemical reaction Energy can be converted from one form to another

8. LE 8-2 On the platform, the diver has more potential energy. Diving converts potential energy to kinetic energy. Climbing up converts kinetic energy of muscle movement to potential energy. In the water, the diver has less potential energy.

9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The First Law of Thermodynamics According to the first law of thermodynamics, the energy of the universe is constant – Energy can be transferred and transformed – Energy cannot be created or destroyed The first law is also called the principle of conservation of energy

10. LE 8-3 Chemical energy Heat CO 2 First law of thermodynamicsSecond law of thermodynamics H2OH2O

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Exergonic and Endergonic Reactions in Metabolism An exergonic reaction proceeds with a net release of free energy and is spontaneous An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous

12. LE 8-6a Reactants Energy Products Progress of the reaction Amount of energy released (  G < 0) Free energy Exergonic reaction: energy released

13. LE 8-6b Reactants Energy Products Progress of the reaction Amount of energy required (  G > 0) Free energy Endergonic reaction: energy required

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) is the cell’s energy shuttle ATP provides energy for cellular functions

15. LE 8-8 Phosphate groups Ribose Adenine

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis Energy is released from ATP when the terminal phosphate bond is broken

17. LE 8-9 Adenosine triphosphate (ATP) Energy PP P PP P i Adenosine diphosphate (ADP) Inorganic phosphate H2OH2O + +

18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction Overall, the coupled reactions are exergonic

19. LE 8-10 Endergonic reaction:  G is positive, reaction is not spontaneous Exergonic reaction:  G is negative, reaction is spontaneous  G = +3.4 kcal/mol  G = –7.3 kcal/mol  G = –3.9 kcal/mol NH 2 NH 3 Glu Glutamic acid Coupled reactions: Overall  G is negative; together, reactions are spontaneous AmmoniaGlutamine ATP H2OH2O ADP P i + + +

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How ATP Performs Work ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant The recipient molecule is now phosphorylated The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP

21. LE 8-11 NH 2 Glu P i P i P i P i NH 3 P P P ATP ADP Motor protein Mechanical work: ATP phosphorylates motor proteins Protein moved Membrane protein Solute Transport work: ATP phosphorylates transport proteins Solute transported Chemical work: ATP phosphorylates key reactants Reactants: Glutamic acid and ammonia Product (glutamine) made + + +

22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Regeneration of ATP ATP is a renewable resource that is regenerated by addition of a phosphate group to ADP The energy to phosphorylate ADP comes from catabolic reactions in the cell The chemical potential energy temporarily stored in ATP drives most cellular work

23. LE 8-12 P i ADP Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (energonic, energy- yielding processes) ATP +

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzymes speed up metabolic reactions by lowering energy barriers A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction An enzyme is a catalytic protein Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction

25. LE 8-13 Sucrose C 12 H 22 O 11 Glucose C 6 H 12 O 6 Fructose C 6 H 12 O 6

26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Activation Energy Barrier Every chemical reaction between molecules involves bond breaking and bond forming The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (E A ) Activation energy is often supplied in the form of heat from the surroundings

27. LE 8-14 Transition state CD A B EAEA Products CD A B  G < O Progress of the reaction Reactants C D A B Free energy

28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings How Enzymes Lower the E A Barrier Enzymes catalyze reactions by lowering the E A barrier

29. LE 8-15 Course of reaction without enzyme E A without enzyme  G is unaffected by enzyme Progress of the reaction Free energy E A with enzyme is lower Course of reaction with enzyme Reactants Products

30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Substrate Specificity of Enzymes The reactant that an enzyme acts on is called the enzyme’s substrate The enzyme binds to its substrate, forming an enzyme-substrate complex The active site is the region on the enzyme where the substrate binds Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction

31. LE 8-16 Substrate Active site Enzyme Enzyme-substrate complex

32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Catalysis in the Enzyme’s Active Site In an enzymatic reaction, the substrate binds to the active site

33. LE 8-17 Enzyme-substrate complex Substrates Enzyme Products Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Active site (and R groups of its amino acids) can lower E A and speed up a reaction by acting as a template for substrate orientation, stressing the substrates and stabilizing the transition state, providing a favorable microenvironment, participating directly in the catalytic reaction. Substrates are converted into products. Products are released. Active site is available for two new substrate molecules.

34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Effects of Local Conditions on Enzyme Activity An enzyme’s activity can be affected by: – General environmental factors, such as temperature and pH – Chemicals that specifically influence the enzyme

35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Effects of Temperature and pH Each enzyme has an optimal temperature in which it can function Each enzyme has an optimal pH in which it can function

36. LE 8-18 Optimal temperature for typical human enzyme Optimal temperature for enzyme of thermophilic (heat-tolerant bacteria) Temperature (°C) Optimal temperature for two enzymes 020 40 6080100 Rate of reaction Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) pH Optimal pH for two enzymes 0 Rate of reaction 1 23 45 67 8 910

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cofactors Cofactors are nonprotein enzyme helpers Coenzymes are organic cofactors

38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Enzyme Inhibitors Competitive inhibitors bind to the active site of an enzyme, competing with the substrate Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective

39. LE 8-19 Substrate Active site Enzyme Competitive inhibitor Normal binding Competitive inhibition Noncompetitive inhibitor Noncompetitive inhibition A substrate can bind normally to the active site of an enzyme. A competitive inhibitor mimics the substrate, competing for the active site. A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions.

40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allosteric Regulation of Enzymes Allosteric regulation is the term used to describe cases where a protein’s function at one site is affected by binding of a regulatory molecule at another site Allosteric regulation may either inhibit or stimulate an enzyme’s activity

41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Allosteric Activation and Inhibition Most allosterically regulated enzymes are made from polypeptide subunits Each enzyme has active and inactive forms The binding of an activator stabilizes the active form of the enzyme The binding of an inhibitor stabilizes the inactive form of the enzyme

42. LE 8-20a Allosteric enzyme with four subunits Regulatory site (one of four) Active form Activator Stabilized active form Active site (one of four) Allosteric activator stabilizes active form. Non- functional active site Inactive form Inhibitor Stabilized inactive form Allosteric inhibitor stabilizes inactive form. Oscillation Allosteric activators and inhibitors

43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cooperativity is a form of allosteric regulation that can amplify enzyme activity In cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits

44. LE 8-20b Substrate Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation. Cooperativity another type of allosteric activation Stabilized active form Inactive form

45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Feedback Inhibition In feedback inhibition, the end product of a metabolic pathway shuts down the pathway Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed

46. LE 8-21 Active site available Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Enzyme 2 Intermediate A Isoleucine used up by cell Feedback inhibition Active site of enzyme 1 can’t bind theonine pathway off Isoleucine binds to allosteric site Enzyme 3 Intermediate B Enzyme 4 Intermediate C Enzyme 5 Intermediate D End product (isoleucine)